tbuckley/cabot-search huggingface dataset:
P01.15.A Longitudinal assessment of neurocognition and quality of life in low-grade glioma patients receiving first-line Temozolomide
Authors: A Darlix, M Fabbro, M Monnier, F Castan, L Coutant, E Denis, M Carriere, N Menjot de Champfleur, V Rigau, H Duffau, E Guerdoux
Journal: Neuro-Oncology (2022)

Abstract Background While maximal safe resection is the first therapeutic option in patients with newly-diagnosed diffuse low-grade glioma (DLGG), the timing and choice of further treatments (chemotherapy, radiation therapy or combinations of both) remain controversial. Because the expected survival is long in these young patients, the oncological impact of treatments must be balanced with the possible side effects, in particular regarding neurocognitive functioning and quality of life (QoL). Temozolomide (TMZ), an alkylating agent, is widely used in this setting. Here we aimed at evaluating the feasibility of a longitudinal neurocognitive and QoL assessment in DLGG patients receiving TMZ. Material and Methods We conducted a prospective study including adult DLGG patients receiving TMZ as first-line treatment after surgical resection(s) or biopsy. Neurocognition and QoL were evaluated longitudinally until progression. The feasibility was evaluated in terms of participation and compliance of a complete neurocognitive and QoL assessment (defined as the completion of these assessments at baseline, 6 months and 12 months). Secondary objectives were the description of the proportion of patients with changes in neurocognitive or QoL scores on TMZ. Results Of 29 eligible patients, 26 accepted to enter the study (participation rate 86.7%): 57.7% men, median age 45y. Tumor type was distributed as follows: astrocytoma, IDH-mutant 13/26, astrocytoma, IDH wild-type 1/26 and oligodendroglioma, IDH mutant and 1p19q codeleted 12/26. The compliance rate was 95.6% (evaluable in 23 patients as 3 patients had tumor progression within the first 12 months of TMZ). After TMZ, 13.6% of patients experienced a decline of the MoCA score as compared to baseline (from normal to abnormal). Cognitive complaints according to the FACT-COG assessment were stable for 90.9%. The complete cognitive and QoL evaluations (baseline and after 12 months of TMZ) will be presented. Conclusion Our data shows that a longitudinal evaluation of cognition and QoL is feasible in low-grade glioma patients. It suggests that first-line TMZ does not negatively affect neurocognition and QoL. These results must be evaluated in the long-term setting (evaluations ongoing) and confirmed in a larger, multicenter cohort.
JS04.4.A Beyond β-catenin: Genetic alterations of<i>TP53</i> and<i>OTX2</i> and older age indicate increased risk of relapse in WNT medulloblastomas
Authors: T Goschzik, M Mynarek, E Doerner, I Spier, M Warmuth-Metz, B Bison, D Obrecht, N Struve, R Kortmann, P Hau, S Aretz, S Rutkowski, T Pietsch
Journal: Neuro-Oncology (2022)

Abstract Background This genetic analysis of WNT-activated medulloblastomas (WNT-MBs) aimed to re-evaluate the prognostic impact of age, TP53 mutations and to identify specific chromosomal aberrations as possible prognostic markers. Material and Methods In a cohort of 191 patients with WNT-MBs, mutations in CTNNB1, APC and TP53 were analyzed by Sanger and/or NGS panel sequencing. Chromosomal copy number aberrations were assessed by high-resolution, genome-wide molecular inversion probe technology (MIP), SNP6 array, and/or 850k methylation bead-array hybridization. Association with prognosis was evaluated in 133 patients with follow-up data from the HIT2000 medulloblastoma trial, HIT registries, and the NOA-07 trial. Results CTNNB1 mutations were present in 92.2% of the samples. APC mutations were found in 6.8% (13 samples). One CTNNB1 wildtype tumor gained WNT-activation due to a homozygous deletion of FBXW7. Monosomy 6 was present in 78.6%, and more frequent in children compared to adolescents/adults (≥16 years). Adolescents/adults showed worse overall survival (OS; p=0.009) compared to children, but not worse progression-free survival (PFS; p=0.106). With an age cut-off at 18 years, no survival difference was found. Also adolescents alone (16-20 years) had worse OS (p=0.003) compared to children, whereas in patients ≥21 (n=12 adults with PFS/OS data) no tumor progression/relapse occurred. Only one adult died due to therapy-related complications. WNT-MB patients with tumors harboring TP53 mutations (24/133, 18.1%) showed significant worse PFS (p=0.001), which was also found in children and adolescents individually (p=0.004, resp. p=0.017). Gains of the OTX2 locus on chromosome 14q found in 40.2% (35/87) of samples were independent of TP53 mutations and also associated with poor PFS and OS (p=0.034, resp. p=0.016). Individual analyses of OTX2 gains within age groups showed only worse OS in children (p=0.012). Multivariate Cox regression analysis for PFS identified both genetic alterations, but not age, as independent prognostic markers. For OS, multivariate analysis found OTX2 gains and older age as independent prognostic markers. Conclusion Our data suggest that adolescent patients with WNT-MB and those patients carrying TP53 mutations or OTX2 gains - independent of age - are at higher risk of relapse. Eligibility of these patients for therapy de-escalation trials needs to be debated.
KS04.6.A Epidemiology of adult meningioma in the Netherlands: a population-based study
Authors: V K Y Ho, M M Anten, A Garst, E M Bos, T J Snijders, D B P Eekers, T Seute
Journal: Neuro-Oncology (2022)

Abstract Background Meningiomas are the most common primary tumours of the central nervous system. As the majority of meningiomas are benign, initial management often consists of observation only. Consequently, estimates on meningioma incidence are generally considered too low, with many registries mainly depending on pathology notifications. With additional notification sources, this study provides more complete population-based estimates on the incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands. Material and Methods Data on patients diagnosed with meningioma during 2000-2019 were obtained from the Netherlands Cancer Registry (NCR), which was expanded to the Dutch Brain Tumour Registry (DBTR) for meningiomas as of 2016. In addition to histological confirmations, the NCR/DBTR receives case notifications from hospital administrative registrations on cost reimbursement and outpatient care. In addition, a data linkage was performed with a clinical database maintained by one of the Dutch neuro-oncology centres to evaluate local completeness of the NCR/DBTR. Time trends of the age-adjusted incidence rates were evaluated by calculating the estimated annual percentage change (EAPC). Relative survival rates were calculated using the Pohar-Perme estimator. Results From 2000 to 2019, a total of 22,605 cases of meningioma were registered; 11,423 (50.5%) were histologically confirmed, while 11,182 (49.5%) had a radiological diagnosis. Over time, incidence increased from 4.7 per 100,000 inhabitants (European Standardized Rate, ESR) to 10.7 (EAPC 4.6%, p&amp;lt;0.01); the incidence of radiological diagnosis increased from 1.2 to 6.9 per 100,000 ESR (EAPC 9.6%, p&amp;lt;0.01). Local data completeness was estimated at 98% for histologically confirmed meningiomas and 87% for radiological diagnoses. On the basis of these incidence estimates, the prevalence of meningioma is estimated at 105/100,000 on January 1st of 2020, with over 17,500 individuals having had a diagnosis of meningioma at that moment. Relative survival rate at 5 years for grade I meningiomas was 94.8% (95%-confidence interval: 94.0%-95.4%), 84.0% (95%CI: 81.0%-86.5%) for grade II meningiomas, and 47.3% (95%CI: 38.2%-55.8%) for grade III meningiomas. Conclusion As the incidence estimates in this study may be considered most complete, the results obtained should approximate the true incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands.
P10.20.A Mechanisms of synergistic glioma growth suppression by radiotherapy and MET inhibition
Authors: M Silginer, E Papa, E Szabo, F Vasella, M Pruschy, C Stroh, P Roth, T Weiss, M Weller
Journal: Neuro-Oncology (2022)

Abstract Background Glioblastoma remains to be one of the most lethal solid cancers. Despite multi-modal therapy including surgery as safely feasible, radiotherapy and chemotherapy with the alkylating agent temozolomide, the median survival of affected patients is still limited to approximately one year on a population level. Thus, novel therapies are urgently needed. There is increasing interest in the role of the HGF/MET pathway in the response of glioblastoma to radiotherapy since MET may be involved in radioresistance via proinvasive and DNA damage response pathways. Material and Methods Here we assessed the role of the MET pathway in the response to radiotherapy in vitro and in vivo in syngeneic mouse glioma models and explored potential modes of action responsible for the synergistic effects of MET pathway inhibition and irradiation on tumor growth in vivo. Results Murine glioma cells express HGF and MET and show increased MET phosphorylation upon exposure to exogenous HGF. In vitro, glioma cell viability and proliferation are not affected by pharmacological MET inhibition using tepotinib or genetic MET inhibition using CRISPR/Cas9-engineered Met gene knockout and sensitization to irradiation by MET inhibition is not seen. In vivo, the combination of MET inhibition with focal radiotherapy mediates prolonged survival of syngeneic orthotopic glioma-bearing mice compared with either treatment alone. Complementary studies demonstrate that synergy is lost when gliomas are established and treated in immunodeficient mice, but also if MET gene expression is disrupted in the tumor of wildtype mice. Combination therapy suppresses a set of pro-inflammatory mediators that are upregulated by radiotherapy alone and which are positively regulated by transforming growth factor (TGF)-β. In line with this data, ex vivo analysis of mouse brains reveal increased TGF-β pathway activity upon irradiation alone that is counteracted by concomitant MET inhibition. Conclusion In summary, we demonstrate synergistic suppression of syngeneic glioma growth by irradiation and MET inhibition that requires MET expression in the tumor as well as an intact immune system. Clinical evaluation of this combined treatment approach in newly diagnosed glioblastoma is warranted.
P10.23.B Polycystin-1 induces mechanotransduction pathways in gioblastoma cells under hydrostatic pressure
Authors: I Zoi, A Gargalionis, K Papavassiliou, N Nasiri-Ansari, C Piperi, E Basdra, A Papavassiliou
Journal: Neuro-Oncology (2022)

Abstract Background Increased mechanical load and stiffness of the tumor microenvironment are key features during progression of gliomas. Polycystin-1 (PC1) is a mechanosensitive protein which perceives extracellular mechanical cues. The aim of the study was to investigate PC1 participation in mechanisms of glioblastoma (GBM) progression under a mechanically-induced microenvironment. Material and Methods We generated monolayer cell cultures and tumor spheroids of the T98G glioblastoma cell line. Cells were subjected to continuous hydrostatic pressure (HP), inhibition of PC1 mechanical perception through functional blockage of its extracellular domain, and silencing of PKD1 expression. The level of activation of PC1 mechano-induced downstream kinases (mTOR, ERK, FAK) and transcription factors (YAP, TAZ) was evaluated via Western blot at specific time-points. Functional assays were performed to assess cell proliferation, clone formation, and cell migration. qPCR was employed to quantify the mRNA expression of markers regarding certain traits of cancer cells. Results In monolayer cell cultures, PC1 functional inhibition under HP is associated with mTOR and ERK activation and elevated expression of TAZ. On the other hand, PKD1 knockdown under HP is associated with activation of FAK, but not mTOR or ERK. In tumor spheroids, PC1 inhibition acts in synergy with HP to activate FAK and upregulate YAP, but not ERK or mTOR. PC1 inhibition under HP is associated with compact 3-dimensional spheroid structures. PC1 inhibition acts in synergy with HP to suppress cell proliferation, clone formation, and cell migration in GBM cells. The same synergistic effect is observed on the expression of respective markers of apoptosis, angiogenesis, proliferation, and epithelial-to-mesenchymal transition of GBM cells. Conclusion PC1 seems to be able to sense applied mechanical forces in GBM cells by regulating the activity of downstream molecules and enhance certain traits of tumor promotion. This work was co-financed by Operational Programme “Human Resources Development, Education and Lifelong Learning”, National Strategic Reference Framework (NSRF) 2014-2020, Ministry of Economy and Development, Greece &amp; European Union (European Social Fund (ESF), in the context of the project “Investigation of the role of polycystin proteins in glioma neoplastic cells”; Grant/Award Number: MIS 5047967
P07.02.B Neuro-oncological augmented reality planning (NOA-p)
Authors: F Van Gestel, T Frantz, Q Neuville, S Klein, M Bruneau, B Jansen, T Scheerlinck, J Vandemeulebroucke, J Duerinck
Journal: Neuro-Oncology (2022)

Abstract Background When preparing for the resection of an intracranial lesion, neuronavigation with a tracked pointer is most often used to determine lesion borders and the optimal approach. This can sometimes prove challenging, especially for deep-seated lesions. Augmented Reality (AR), directly displaying the lesion on the patient’s skin, can simplify and improve this step. Material and Methods We developed a system for inside-out infrared tracking that does not require an external tracking camera or external computer and allows for heads-up displaying an AR scene on the Microsoft HoloLens II. Twenty patients planned for the resection of an intracerebral lesion were included in our study. After patient registration, the lesion outlines were marked on the patient’s skin by different participants, consecutively using the Brainlab neuronavigation system and the HoloLens. Each registration on both systems provided a registration transform that was compared for accuracy and consistency. The performance of the participants was measured in terms of duration and accuracy and compared to expert registration and delineation. Results Both registration and delineation were significantly faster with AR (p=0.02 and p&amp;lt;0.001, respectively, and p&amp;lt;0.001 for the total duration), taking 79.23±17.48 and 39.58±39.10 seconds while neuronavigation required 96.61±24.54 and 90.80±44.09 seconds. AR had a registration offset of 3.3mm and 3.4°, and was more consistent compared to neuronavigation. AR facilitated more accurate and detailed lesion delineation, while neuronavigation often overestimated lesion size. Conclusion Augmented reality provides a faster and more accurate alternative for resection planning. Lesion delineation is more intuitive while remaining high in accuracy. Future research should focus on further intraoperative implementations.
KS02.6.A Application of positive psychology intervention in continuous quality improvement of nursing care for patients with intracranial tumor
Authors: L Bai, Z Zhou
Journal: Neuro-Oncology (2022)

Abstract Background To investigate the effect of positive psychology intervention on continuous quality improvement of nursing care for patients with intracranial tumor Material and Methods A total of 124 patients with intracranial tumor who received surgical treatment in our hospital from October 2020 to December 2021 were selected by convenience sampling method, and the patients were randomly divided into control group and intervention group.Patients in the control group received continuous quality improvement of postoperative routine care, and patients in the intervention group received positive psychological intervention based on postoperative routine care. Postoperative treatment compliance, subjective well-being and daily living ability were compared between the two groups Results The excellent compliance rate of intervention group was 95.15%, significantly higher than that of control group 83.87% (P &amp;lt; 0.05). The subjective well-being in intervention group (56.73±3.42) was significantly higher than that in control group (53.81±2.76) (P &amp;lt; 0.05). There was no significant difference in daily living ability score between 2 groups before intervention (P &amp;gt; 0.05). After intervention, the daily living ability score of the intervention group was (57.49±9.16), which was significantly higher than that of the control group and before intervention (P &amp;lt; 0.05). Conclusion Positive psychology intervention for patients with intracranial tumor can effectively improve the quality of nursing, increase the patient's treatment compliance, and improve the subjective well-being of patients and the ability of daily life is of great significance.
PL01.6.A Radiomics outperforms semantic features for prediction of response to stereotactic radiosurgery in brain metastases
Authors: R Gutsche, P Lohmann, M Hoevels, D Ruess, N Galldiks, V Visser-Vandewalle, H Treuer, M I Ruge, M Kocher
Journal: Neuro-Oncology (2022)

Abstract Background Brain metastases show different patterns of contrast enhancement, potentially reflecting hypoxic and necrotic tumor regions with reduced radiosensitivity. An objective evaluation of these patterns might allow a prediction of response to radiotherapy. We therefore investigated the potential of MRI radiomics in comparison with the visual assessment of semantic features to predict early response to stereotactic radiosurgery in patients with brain metastases. Material and Methods In this retrospective study, 150 patients with 308 brain metastases from solid tumors (NSCLC in 53% of patients) treated by stereotactic radiosurgery (single dose of 17-20 Gy) were evaluated. The response of each metastasis (partial or complete remission vs. stabilization or progression) was assessed within 180 days after radiosurgery. Patterns of contrast enhancement in the pre-treatment T1-weighted MR images were either visually classified (homogenous, heterogeneous, necrotic ring-like) or subjected to a radiomics analysis. Random forest models were optimized by cross-validation and evaluated in a hold-out test data set (30% of metastases). Results In total, 221/308 metastases (72%) responded to radiosurgery. The optimal radiomics model comprised 10 features and outperformed the model solely based on semantic features in the test data set (AUC, 0.71 vs. 0.56; accuracy, 69% vs. 54%). The diagnostic performance could be further improved by combining semantic and radiomics features resulting in an AUC of 0.74 and an accuracy of 75% in the test data set. Conclusion The developed radiomics model allowed prediction of early response to radiosurgery in patients with brain metastases and outperformed the visual assessment of patterns of contrast enhancement.
OS03.4.A <i>In vivo</i> dynamics and anti-tumor effects of EpCAM-directed CAR T-cells against brain metastases from lung cancer
Authors: T Xu, P Karschnia, B Cadilha, S Dede, M Lorenz, N Seewaldt, E Nikolaishvili, K Müller, J Blobner, N Teske, S Langer, H Obeck, T Lorenzini, M Mulazzani, W Zhang, H Ishikawa-Ankerhold, V R Buchholz, M Subklewe, N Thon, A Straube, J Tonn, S Kobold, L von Baumgarten
Journal: Neuro-Oncology (2022)

Abstract Background Lung cancer patients are at a particularly high risk for brain metastases, and a considerable number of affected patients succumb due to their intracranial disease. Chimeric Antigen Receptor (CAR) T-cells emerged as a powerful class of cell-based immunotherapy for hematological malignancies. However, it remains unclear whether CAR T-cells also represent a safe and effective therapeutic option for brain metastases. Material and Methods A fully syngeneic orthotopic cerebral metastasis model in mice was established by combining a chronic cranial window with repetitive intracerebral two-photon laser scanning microscopy. This approach enabled the in vivo characterization of red fluorescent CAR T-cells and tumor cells on a single-cell level over weeks. Intraparenchymal injection of Lewis lung carcinoma cells (expressing the tumor cell-antigen EpCAM) was performed, and CAR T-cells directed against EpCAM (EpCAMCAR T-cells) were injected into the adjacent brain parenchyma after solid brain tumors have formed. Results All mice had visible tumor take four days after the intracranial tumor cell injection, and rapid growth of solitary lesions was seen in the following days. No toxicities mediated by intracranially injected EpCAMCAR T-cells were encountered. In mice treated with EpCAMCAR T-cells, we initially observed substantial CAR T-cell accumulation within the tumor compared to controls (median number: 1700 versus 939 cells/mm2; p = 0.007). This was paralleled by lower velocities of EpCAMCAR T-cells, characterizing T-cell receptor (TCR)-mediated antitumor cytotoxicity due to long-lasting contacts between effector immune cells and tumor cells. Consequently, treatment with EpCAMCAR T-cells resulted in reduced tumorous growth as determined per in vivo microscopy (median tumor area on day 10: 1.8 versus 10.8 mm2; p = 0.001) and immunohistochemistry of excised brains (median tumor volume on day 10: 3.6 versus 33.2 mm3; p = 0.001). However, the number of EpCAM-directed CAR T-cells within the tumor markedly decreased during the observation period, pointing towards insufficient persistence of EpCAM-directed CAR T-cells. In line with these findings, survival was prolonged in mice receiving EpCAMCAR T-cells but long-lasting remission was rare (median survival: 15 versus 13 days; p = 0.012). Conclusion Our findings indicate that CAR T-cells injected into the cerebral parenchyma may induce relevant anti-tumor effects in brain metastases from lung cancer. Due to the translational nature of our study, prospective clinical cohorts appear warranted. Strategies improving the intratumoral persistence of CAR T-cells in brain metastases may be utilized to further boost the success of such promising therapy.